Clinical Trials

MainTitle

Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified December 2017 by University of Colorado, Denver

Sponsor
University of Colorado, Denver


Information provided by (Responsible Party)
University of Colorado, Denver
ClinicalTrials.gov Identifier
NCT03126370

First received: April 19, 2017
Last updated: December 1, 2017
Last Verified: December 2017
History of Changes
Purpose

Purpose

This study will evaluate the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide (TAF). Subjects living with human immunodeficiency virus (HIV) who are receiving tenofovir-based antiretroviral therapy (in the form of tenofovir disoproxil fumarate [TDF]), and are also taking a ritonavir- or cobicistat-boosted protease inhibitor will be invited to participate.

The study will consist of five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and one end-of-study follow-up visit.

Subjects will also be asked to use a Wisepill device, which will track medication adherence throughout the study.

Condition Intervention Phase
Hepatitis C
HIV Coinfection

Drug : LDV/SOF and TAF
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures

  • Change in area under the plasma concentration (AUC) of tenofovir [ Time Frame: Over the course of 40 weeks, will be assessed at 12 weeks, 24 weeks, 28 weeks, and 40 weeks. ]
    Compare tenofovir AUC0-24 before and after switching from TDF to TAF, and before and after administration of LDV/SOF
  • Change in tenofovir diphosphate in peripheral blood mononuclear cells [ Time Frame: Over the course of 40 weeks, will be assessed at 12 weeks, 24 weeks, 28 weeks, and 40 weeks. ]
    Compare tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMC's) when tenofovir is given as TDF and then switched to TAF and also when TAF is given with LDV/SOF
Secondary Outcome Measures:
  • Change in tenofovir diphosphate in dried blood spots [ Time Frame: 24 and 28 weeks ]
    Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) when tenofovir is given as TDF and then switched to TAF and also when TAF is given with LDV/SOF
  • Change in Estimated Glomerular Filtration Rate (eGFR), urinary retinol binding protein/creatinine ratios, and urinary beta-2 microglobulin/creatinine ratios [ Time Frame: Over the course of 40 weeks, will be assessed at 12 weeks, 24 weeks, 28 weeks, and 40 weeks. ]
    Compare eGFR calculated using Modification of Diet in Renal Disease (MDRD) equation and other renal safety markers before and after the addition of LDV/SOF

Estimated Enrollment: 15
Anticipated Study Start Date: January 2018
Estimated Study Completion Date: August 31, 2019
Estimated Primary Completion Date: August 31, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: LDV/SOF and TAF
Subjects who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Subjects will then be switched to tenofovir alafenamide 25mg/emtricitabine 200mg (Descovy) with for an additional 12 weeks. After taking tenofovir alafenamide/emtricitabine for 12 weeks, subjects will then start taking ledipasvir 90mg/sofosbuvir 400mg (Harvoni) in combination with the tenofovir alafenamide 25mg/emtricitabine 200mg (Descovy) for 4 weeks. Subjects will then return to taking tenofovir alafenamide 25mg/emtricitabine 200mg (Descovy) for an additional 12 weeks.
Drug: LDV/SOF and TAF
  • Subjects will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide. Once on tenofovir alafenamide for 12 weeks, subjects will be given concominant ledipasvir/sofosbuvir for 4 weeks, then revert to tenofovir alafenamide for the final 12 weeks.
  • Other: Blood draws for tenofovir PK, renal function assessment

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 70 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • Between 18-70 years of age
  • Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV


Exclusion Criteria:
  • eGFR < 30 mL/min
  • Pregnant or planning pregnancy
  • Breastfeeding
  • Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
  • Signs or symptoms of decompensated liver disease
  • Hepatitis B infection
  • Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide
  • Unwillingness or inability to comply with study procedures
  • Chronic hepatitis C infection

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03126370

Contacts

Contact:   Jennifer J Kiser, PharmD 303-724-6131 jennifer.kiser@ucdenver.edu
Contact:   Kristina M Brooks, PharmD 303-724-0395 kristina.brooks@ucdenver.edu

Locations

United States, Colorado
University of Colorado Hospital Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Jennifer J Kiser, PharmD    303-724-6131    jennifer.kiser@ucdenver.edu
Contact: Kristina M Brooks, PharmD    303-724-0395    kristina.brooks@ucdenver.edu

Sponsors and Collaborators

University of Colorado, Denver

Investigators

Principal Investigator: Jennifer J Kiser, PharmD University of Colorado, Denver
More Information

More Information


Responsible Party: University of Colorado, Denver  
ClinicalTrials.gov Identifier: NCT03126370   History of Changes  
Other Study ID Numbers: 17-0490  
Study First Received: April 19, 2017  
Last Updated: December 1, 2017  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: No  

Additional relevant MeSH terms:
Hepatitis C
Coinfection
Tenofovir
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination

ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.